| First Author | DeWard AD | Year | 2009 |
| Journal | PLoS One | Volume | 4 |
| Issue | 9 | Pages | e7102 |
| PubMed ID | 19768111 | Mgi Jnum | J:153615 |
| Mgi Id | MGI:4365868 | Doi | 10.1371/journal.pone.0007102 |
| Citation | DeWard AD, et al. (2009) Loss of RhoB expression enhances the myelodysplastic phenotype of mammalian diaphanous-related Formin mDia1 knockout mice. PLoS One 4(9):e7102 |
| abstractText | Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis and hyperplastic bone marrow. Complete loss or interstitial deletions of the long arm of chromosome 5 occur frequently in MDS. One candidate tumor suppressor on 5q is the mammalian Diaphanous (mDia)-related formin mDia1, encoded by DIAPH1 (5q31.3). mDia-family formins act as effectors for Rho-family small GTP-binding proteins including RhoB, which has also been shown to possess tumor suppressor activity. Mice lacking the Drf1 gene that encodes mDia1 develop age-dependent myelodysplastic features. We crossed mDia1 and RhoB knockout mice to test whether the additional loss of RhoB expression would compound the myelodysplastic phenotype. Drf1(-/-)RhoB(-/-) mice are fertile and develop normally. Relative to age-matched Drf1(-/-)RhoB(+/-) mice, the age of myelodysplasia onset was earlier in Drf1(-/-)RhoB(-/-) animals--including abnormally shaped erythrocytes, splenomegaly, and extramedullary hematopoiesis. In addition, we observed a statistically significant increase in the number of activated monocytes/macrophages in both the spleen and bone marrow of Drf1(-/-)RhoB(-/-) mice relative to Drf1(-/-)RhoB(+/-) mice. These data suggest a role for RhoB-regulated mDia1 in the regulation of hematopoietic progenitor cells. |
